This year we initiated experiments examining the effects of methamphetamine on the HIV long terminal repeat (LTR) promoter in primary microglia, primary neurons and cell lines. We have optimized conditions to isolate microglia from rats. We are currently optimizing gene transfer paradigms to deliver a reporter gene construct to measure the activity of the HIV LTR promoter in the presence of methamphetamine. Using cell lines, we have successfully delivered the reporter construct and are currently preparing our results for publication. This work is ongoing. One of the proteins that our section has been studying for many years is bone morphogenetic protein 7, specifically, its neurotrophic/neuroregenerative properties. We previously demonstrated that exogenous application of bone morphogenetic protein 7 (BMP7) reduced 6-hydroxydopamine-mediated neurodegeneration in a rodent model of Parkinson's disease. Recently, we are examining the cellular and molecular mechanisms of BMP7 neuroregenerative effects by focusing on the ability to influence the extracellular matrix (ECM) or more generally the extracellular environment. Using a primary rat neurons, we are examining BMP7's ability to influence ECM-modifiying enzymes. Collectively, our data demostrate that BMP7 and BMP receptor signaling have neuroprotective and neuroregenerative effects in various models of neurodegeneration. We generated an AAV vector expressing the human mu opioid receptor (huMOR) and are evaluating the role of huMOR in methamphetamine sensitization in mice. Our preliminary findings show that huMOR expression by an AAV vector in specific brain regions alters methamphetamine sensitization. We have submitted this work for publication and it is currently under review. We have also generated an AAV vector expressing the glutamate transporter (GLT-1) and demonstrated that it functional. We have ongoing work examining the ability of GLT-1 to reduce damage caused by ischemia using a rat model of stroke. The protection against ischemia was accompanied by a decrease in ischemia-induced glutamate overflow as measured by microdialysis and this study was published this year. AAV-GLT-1 was created to modulate the levels of extracellular glutamate. We have begun experiments examining the ability of excess GLT-1 overexpression by AAV to reduce excitoxicity by glutamate. We have also begun examining the GLT-1 overexpression in specfic brain regions for alterations to methamphetamine sensitization. These experiments are ongoing. Lastly, we contributed to the completion of a collaborative study with Dr. Yavin Shaham at the NIDA-IRP.